tbuckley/cabot-search huggingface dataset:
Transarterial chemoembolization combined with camrelizumab and apatinib in the treatment of advanced hepatocellular carcinoma: Preoperative or postoperative combination? A prospective clinical study.
Authors: Hui Xie, Yuqing Yang, Yane Liu, Zhenyu Wen, Junxiao Wang
Journal: Journal of Clinical Oncology (2023)

e16150 Background: The timing of the combination of an antiangiogenic agent (apatinib) and an immune checkpoint inhibition inhibitor (camrelizumab) in patients with advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is unclear. Therefore, this study aims to evaluate the efficacy and safety of TACE combined with camrelizumab and apatinib for advanced hepatocellular carcinoma (HCC), and to explore the timing of the combination therapy. Methods: The institutional Review Board approved our study and registered it in the Chinese Clinical Trial Registry (ChiCTR2000034155). Between June 2020 and January 2022, we prospectively recruited patients with unresectable HCC not receiving systemic therapy and randomly divided them into preoperative and postoperative medication groups according to the timing of drug administration. Patients in the preoperative medication group received camrelizumab 200 mg per 2 weeks intravenously and oral apatinib 250 mg/day orally prior to TACE. Patients in the postoperative medication group received the same dose of camrelizumab and apatinib after recovery of liver function following TACE. The primary endpoint of the study was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results: A total of 33 patients were enrolled in this study. There were 15 patients in the preoperative medication group and 18 patients in the postoperative medication group. Median OS was significantly longer in the postoperative medication group than in the preoperative medication group (20 months vs. 12 months; P = 0.034). Patients in the postoperative medication group achieved a higher DCR than that in the preoperative medication group [17 cases (94.4%) vs. 10 cases (66.7%), P = 0.039] Multivariate Cox regression analysis showed that post-TACE combination of apatinib and camrelizumab provided better OS than pre-TACE combination drug therapy (HR = 0.353, 95% CI:0.131-0.953, P = 0.040). No serious adverse events were observed in the two groups. Conclusions: TACE combined with apatinib and camrelizumab treatment in the patients with advanced HCC showed promising efficacy and a manageable safety profile. Compared to pre-TACE with apatinib plus camrelizumab, post-TACE with apatinib plus camrelizumab significantly improved OS and DCR in patients with advanced HCC. Clinical trial information: ChiCTR2000034155 . [Table: see text]
Selection biases in the systematic collection of breast biobank specimens.
Authors: Yael Bar, Gary X. Wang, Gabrielle E. Gioia, Veerle I. Bossuyt, Shirley Shinn-Huey Chou, Steven J. Isakoff, Beverly Moy, Leif W. Ellisen, Constance Dobbins Lehman, Laura Spring
Journal: Journal of Clinical Oncology (2023)

6533 Background: A breast biopsy tissue biobank is a valuable resource for studying breast cancer biology and treatment response. However, underrepresentation of patient populations in biobanks limits the generalizability of findings. The aim of this study was to assess potential age and racial/ethnic disparities in the recruitment process for an institutional breast biopsy tissue bank. Methods: Ultrasound-guided (USG) research biopsy cores were collected immediately after routine clinical biopsy from January 2019 to October 2022 at a large academic center. Study eligibility included patients (pts) aged &gt; 18 years undergoing USG clinical breast biopsy with a radiographically evident mass ≥ 0.6 cm in the longest dimension. Eligible pts, identified by a research associate on the day of the biopsy, were invited to participate at the discretion of the radiologist performing the biopsy. Those approached either consented or declined a research biopsy. Demographic and clinical data of eligible pts were extracted from the EMR. Results: 2449 pts underwent USG breast biopsy and 1309 were deemed eligible for a research biopsy. Of the eligible population, 564 (43%) consented to the study, 322 (25%) declined, and 423 (32%) were not approached. Consented pts were younger compared to those who declined or to those not approached (median age 49, 51, and 51 years, respectively; p = .01). Comparison of study groups by age and race categories are shown in the table. Pts &gt; 70 were less likely to be approached compared to pts &lt; 70 (p = .01). However, The likelihood of pts being approached to consent did not differ significantly with age (p=.09 ). Of the eligible pts, 951 (73%) were White, 327 (25%) were non-White (10% Asian, 8% Black, 1% Hispanic, and 7% other race), and race was unknown for 31 (2%) pts. White and non-White pts were equally likely to be approached (p = .3). However, approached non-White pts were significantly less likely to consent compared to White pts (p =.01). Within the non-White population, Black pts were more likely to decline a research biopsy, with only 50% of approached Black pts consenting compared to 66% of White pts, 61% of Asian pts and 55% of pts of other race. Conclusions: We found disparities based on age and race/ethnicity in participation in a breast biopsy tissue biobank. Older pts were less likely to be offered participation but equally likely to consent when invited, while Black pts were equally likely to be offered participation, but less likely to consent when invited, compared to other racial subgroups. Our findings support targeted interventions to increase participation across diverse subgroups of pts. [Table: see text]
H3.3-K27M neoantigen vaccine elicits anti-tumor T cell immunity against diffuse intrinsic pontine glioma: The phase I ENACTING trial.
Authors: Yang Zhang, Nan Ji, Gang Chen, Haiyang Wu, Yi Wang, Xiao’ou Li, Ling Peng, Wei Xu, Tian Li, Yi Wang, Li-Feng Zhang, Shengjun Sun, Xiaobin Zhao, Si Li, Frank Su, Qi-Jing Li, Liwei Zhang
Journal: Journal of Clinical Oncology (2023)

2052 Background: Diffuse intrinsic pontine glioma (DIPG) harboring H3.3-K27M mutation is a malignant pediatric brain tumor with a &gt;90% mortality rate within two-year of diagnosis. Current therapeutic options for DIPG are limited. Aiming to improve therapeutic outcomes, we herein report the preliminary findings of a phase I trial studying a neoantigen peptide vaccine targeting H3.3-K27M. Methods: ENACTING is an open-label, single center, two-armed phase 1 trial to assess the safety and T cell immunity of a neoantigen peptide vaccine against H3.3-K27M. Patients aged ≥ 5 years old with newly diagnosed DIPG were consented and screened. HLA-A*02+/H3.3-K27M+ patients were enrolled to a two-arm study: Arm A consists of subjects receiving open debulking surgery, and Arm B consists of subjects without surgery eligibilities who received stereotactic biopsy. All patients subsequently received conformal radiotherapy and neoantigen vaccine treatment designed to elicit both CD4+ and CD8+ T cell immune response. Vaccine was administered intramuscularly in combination with polyinosinic-polycytidylic acid-poly-L-Iysine carboxymethylcellulose (Poly-ICLC). The primary objective is to evaluate the safety (AEs graded by CTCAE v4.03) and survival outcomes. Secondary objectives include maximum tolerated dose (MTD) and immunological responses. Results: As of Jan 2023, 11 patients have been treated, with 7 in Arm A and 4 in Arm B. No grade 3-4 treatment-related adverse events have been observed, with fever (81.9%) and injection site pain (54.5%) being the most common AEs. Among 10 efficacy-assessable patients, median progression-free survival (mPFS) and median overall survival (mOS) were 11.4 months (95% CI: 5.8~14.7) and 15.4 months (95% CI: 7.53~not reached), respectively. One-year OS rate was 66.7% (95% CI: 42~100%). One patient was assessed as complete response (CR). T cell responses against neoantigen were detected and H3.3-K27M mutation-specific CD4 + and CD8 + TCR clones were validated. Conclusions: The H3.3-K27M neoantigen vaccine was well tolerated. Initial results from this ongoing study suggest that, compared with other current therapies against DIPG, H3.3-K27M peptide vaccination may provide superior patient survival outcomes. Clinical trial information: NCT04749641 . [Table: see text]
Rural cancer care delivery during the COVID-19 pandemic for patients with early-stage cancer.
Authors: Izumi Okado, Michelle Liu, Carry Elhajj, Lynne Wilkens, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2023)

e18566 Background: Cancer mortality rates remain substantially higher among rural populations. Rural-urban disparities in cancer outcomes are partly associated with care delivery challenges in rural areas, and the COVID-19 pandemic may have exacerbated these disparities. Care coordination (CC) is a critical component of patient-centered care; yet, rural patients experience significant CC-related challenges. In this study, we examined patient-reports of CC and time to treatment initiation (TTI) among rural patients with early-stage cancer. Methods: We conducted a cross-sectional survey with 51 patients with early-stage (I-III) cancer receiving active treatment at rural oncology practices between May 2021 and June 2022. Rural was defined using RUCA. Enrolled patients completed the background questionnaire and the Care Coordination Instrument (CCI). A validated instrument, the 29-item CCI assesses overall patient perceptions of CC and three domains of CC (Communication, Navigation, Operational). Items are rated on a 4-point Likert-scale. Data for the urban cohort were derived from historical data. General linear models (GLMs) were used to compare CCI scores between rural and urban patients. Results: The mean age of rural patients was 58.5 (range 24.0-84.0), and 64.7% were female. GI (39.2%) and breast (33.3%) were the most common cancer types. Median time from diagnosis to treatment initiation for rural patients was 61.0 days (IQR: 30.0-65.8), significantly longer compared to the pre-pandemic state registry data. 21.6% of rural patients reported delays in active treatment. Overall, there were no rural-urban differences on the overall perception of CC ( p &gt; .05). However, rural patients reported significantly lower Communication scores ( p = .027). After adjusting for the effects of covariates, rural-urban differences on Communication remained significant ( p = .016). Item-level analyses revealed significant rural-urban differences in specific aspects of CC (e.g., physician-patient communication). CCI scores were not associated with TTI. Conclusions: Our findings indicate that rural patients with early-stage cancer experienced significant delays in treatment initiation during the pandemic, and there were notable differences in Communication aspects of CC between rural and urban patients. Interventions to improve TTI among rural patients are urgently needed to prevent potentially further exacerbating cancer health disparities.
Cost-effective analysis of rotational intraperitoneal aerosol chemotherapy (RIPAC) in patients with platinum-resistant ovarian cancer.
Authors: Soo Jin Park, Juwon Lim, Hee Seung Kim
Journal: Journal of Clinical Oncology (2023)

e17585 Background: We developed RIPAC, which improves distribution and penetration compared to pressurized intraperitoneal aerosol chemotherapy (PIPAC). To introduce this newly developed device in the real world, we analyzed the cost-effectiveness of rotational intraperitoneal aerosol chemotherapy (RIPAC) device to improve quality of life (QoL) compared to conventional palliative chemotherapy for platinum-resistant ovarian cancer patients. Methods: A decision tree was designed to compare the quality-adjusted life year (QALY) and cost consisting of RIPAC and palliative chemotherapy regimens, such as pegylated liposomal doxorubicin (PLD), gemcitabine (GEM), and topotecan (TOP). Also, to reflect the clinician’s variable preferred regimens for palliative chemotherapy, the average direct and indirect medical costs of belotecan, docetaxel, vinorelbine, and vinblastine were also considered in addition to the three regimens (ANY). The model included quality of life which was measured by European Organization for Research and Treatment of Cancer (EORTC)-Quality of life Questionnaire 30 (QLQ-C30) data gathered from previous clinical trial reports on PIPAC and palliative chemotherapy for recurrent ovarian cancer willingness-to-pay (WTP) threshold was set at US$40,000 per quality-adjusted life year saved. Results: To complete three cycles of palliative chemotherapy using PLD, GEM, TOP, and ANY, the total medical costs were US$15,267, US$9,013, US$16,144, and US$12,631, respectively, and the corresponding QALYs for each regimen were 0.633, 0.553, 0.783, and 0.65. Since RIPAC has not yet been introduced into the medical market, when the maximum RIPAC cost is calculated from ANY considering WTP, the cost of RIPAC excluding the ward, outpatient, and anesthesia-related costs among direct medical costs was estimated to be up to US$4,391. Conclusions: The cost-effective analysis results for the palliative treatment of recurrent ovarian cancer implied that RIPAC could be a cost-effective strategy to improve the QoL of platinum-resistant recurrent ovarian cancer patients.
Phase 1b multicenter study to evaluate CHM 1101 in patients with recurrent or progressive glioblastoma.
Authors: Jason Blair Litten, Aravind Ramakrishnan, Stephanie H. Astrow, Cassandra Harrison, Alex Aliki, Behnam Badie
Journal: Journal of Clinical Oncology (2023)

TPS2086 Background: Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor. More than 300,000 new cases are diagnosed globally with over 250,000 deaths each year (Sung H, et al. CA Cancer J Clin. 2021). Patients with recurrent GBM have a poor prognosis, with limited treatment options and a median survival of less than 1 year (Gallego. Curr Oncol, 2015). While prior attempts to treat GBM with chimeric antigen receptor (CAR) T-cells have been limited by tumor heterogeneity, chlorotoxin (CLTX)-directed CAR T-cells in mice demonstrated broad anti-tumor activity and prolonged survival with no off-tumor toxicity or antigen escape (Wang, et al. Sci Transl Med, 2020). CLTX, a 36–amino acid peptide identified in scorpion venom, selectively binds to malignant glioma cells through matrix metalloproteinase-2 (MMP2) and clinical administration of CLTX-based biologics has been well tolerated in patients (Mamelak, et al. J Clin Oncol, 2005, Patil, et al. Neurosurgery, 2019). CHM 1101 is the first CAR T to utilize CLTX as its tumor targeting domain for autologous CAR T-cell therapy. A single-center first-in-human phase 1 study of CHM 1101 in patients with recurrent GBM is ongoing. Methods: Clinical Trial NCT05627323 is a phase 1b, multi-center study of CHM 1101 in adult subjects with MMP2+ recurrent or progressive GBM after standard therapy. After leukapheresis and tumor resection, pts will receive CHM 1101 at Dose Level 1 (240 × 10 6 CAR T cells) or Dose Level 2 (440 x 10 6 d CAR T-cells), divided across 3 once-weekly intracranial (intracavitary and intraventricular) administrations; after disease assessment at 28 days, additional doses of CHM 1101 can be administered on a weekly schedule. Eligible subjects have a prior histologically confirmed diagnosis of a grade 4 GBM, a grade 2 or 3 malignant glioma with radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or a unifocal relapse of GBM. MMP2+ tumor expression is confirmed by IHC (≥20% moderate/high MMP2 score [2+ or 3+]). The primary endpoint is safety; key secondary endpoints include feasibility, progression-free survival, overall survival, response rate (RANO criteria), and cellular kinetics. Recruitment is ongoing. Clinical trial information: NCT05627323 .
Novel deep learning–based prognostic prediction model for colorectal cancer using hematoxylin and eosin–stained whole slide images.
Authors: Teppei Konishi, Mateusz Grynkiewicz, Keita Saito, Takuma Kobayashi, Akiteru Goto, Michinobu Umakoshi, Takashi Iwata, Hiroshi Nishio, Yuki Katoh, Tomonobu Fujita, Tomoya Matsui, Masaki Sugawara, Hiroyuki Sano
Journal: Journal of Clinical Oncology (2023)

3119 Background: Previous studies have shown that the presence or absence of genetic mutations is critical for colorectal cancer prognosis. However, genomic testing can be expensive and difficult to perform on all samples. In contrast, hematoxylin and eosin (H&amp;E) staining is relatively inexpensive and can be performed on all tissue specimens. In this study, we designed a novel prognostic method using spatial image features extracted from H&amp;E–stained whole slide images (WSIs) and genetic mutation prediction neural networks. Methods: We obtained H&amp;E–stained WSIs and data on Microsatellite Instability ( MSI), BRAF, TTN and APC gene mutations from a clinical cohort of 548 patients with The Cancer Genome Atlas (TCGA) Colon adenocarcinoma and rectum adenocarcinoma. We divided them into training (n=361), validation (n=90), and test (n=115) groups. Classification models were trained to predict the presence or absence of MSI, BRAF, TTN, and APC mutations. The model input comprised features of the H&amp;E–stained WSIs, as obtained via a deep learning–based feature extractor. All resultant models were incorporated into a prognostic model (overall survival: &gt; 60 months (low risk)/&lt; 60 months (high risk)). Our prognostic model’s performance was evaluated against TCGA colorectal dataset, and a survival analysis was performed on the model using the Kaplan–Meier method. Finally, we compared our model’s performance with the end–to–end prognostic prediction of a convolutional neural network (CNN) that also used H&amp;E–stained WSIs as input and provided prognostic prediction as output. Results: Our deep learning–based prognostic prediction model achieved an AUC score of 0.834 with a 95% confidence interval (CI) of 0.734–1.000 alongside TCGA dataset; the survival analysis compared the survival distributions of low–risk and high–risk groups, as predicted by our model; a p–value &lt; 0.01 was obtained. The model could classify low– and high–risk patients and accurately predict patient status as alive (low risk) or deceased (high risk) at 60 months. In contrast, the CNN–based model achieved an AUC score of only 0.502 (95% CI: 0.315–0.690) on the same TCGA dataset, and the p–value obtained for it under the Kaplan–Meier log–rank test was greater than 0.5. The CNN–based method was unable to distinguish between low– and high–risk patients, confirming that our method using spatial imaging features extracted from WSIs was a more effective approach. Conclusions: We developed a novel prognostic prediction method using spatial image features extracted from WSIs and genetic mutation prediction neural networks. Our results demonstrated the advantage of using image features over gene mutation data for prognostic prediction in colorectal cancer patients.
The effect of adding a selective FAK inhibitor AMP945 to FOLFIRINOX in a model of pancreatic cancer.
Authors: Christopher Burns, Kendelle Murphy, Terrie-Anne Cock, Mark Devlin, David Herrmann, Paul Timpson
Journal: Journal of Clinical Oncology (2023)

e15128 Background: Pancreatic Cancer (PC) is a one of the leading causes of cancer-related death in the world, with a five-year survival rate of ~11%. The majority of patients present with advanced metastatic disease and are treated with chemotherapy. FOLFIRINOX is the standard-of-care treatment for patients in many countries and has been shown to result in a median overall survival of 11.1 months. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase which transduces signaling from integrin receptors, activated through interactions with the extracellular matrix, to regulate cell survival, proliferation and migration, and is often highly expressed in PC. Inhibition of FAK in preclinical models of PC has been shown to sensitize cells to radiotherapy, immunotherapy and chemotherapy. AMP945 is a potent and selective FAK inhibitor currently undergoing a Phase Ib/IIa trial in PC in combination with gemcitabine and nab-paclitaxel (NCT05355298). We now demonstrate that AMP945, in combination with FOLFIRINOX, can significantly improve survival in mouse models of PC, providing strong rationale for clinical testing of this novel treatment combination. Methods: Patient Derived Xenograft (PDX) models of PC in NOGIL2 mice using TKCC10lo patient derived cells were conducted in both subcutaneous and orthotopic formats. Once the tumor was palpable, AMP945 (10 mg/kg, b.i.d.) was administered for four days. On day 8 oxaliplatin (5 mg/kg) and irinotecan (25 mg/kg) were administered, with leucovorin calcium (100 mg/kg) and fluorouracil (25 mg/kg) being dosed on day 9. The mice were monitored until day 12 and the treatment regimen was repeated for up to 20 cycles, or until the experimental endpoint was reached. At the experimental endpoint the mice were sacrificed, the tumor harvested and analyzed. Results: In the subcutaneous model the combination of AMP945 and FOLFIRINOX increased survival by ~35% compared to FOLFIRINOX alone. In the orthotopic model, median survival was extended by ~30% when using the AMP945/FOLFIRINOX combination, compared to FOLFIRINOX alone. In both models there was a significant reduction in tumor size and clear evidence of on-target FAK inhibition in tumors (reduction in pY 397 FAK levels) in the combination therapy groups. Notably, a significant increase in cleaved caspase-3, a marker of apoptosis, was also apparent in the combination therapy groups. Conclusions: The FAK inhibitor AMP945, given in a pulsed-dosing regimen in combination with FOLFIRINOX, significantly enhances survival in a mouse model of pancreatic cancer by increasing apoptosis and reducing tumor burden, highlighting the potential of this combination in clinical treatment of PC. A clinical study of the combination of AMP945 with FOLFIRINOX is now in planning.